Increased expression and copy number amplification of LINE-1 and SINE B1 retrotransposable elements in murine mammary carcinoma progression
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Alberto Gualtieri1, Federica Andreola2, Ilaria Sciamanna1, Paola Sinibaldi-Vallebona3, Annalucia Serafino2 and Corrado Spadafora1
1 Istituto Superiore di Sanità, Rome, Italy;
2 Institute of Translational Pharmacology, CNR, Rome, Italy;
3 Department of Experimental Medicine and Surgery - University of Rome “Tor Vergata”, Rome, Italy.
Corrado Spadafora, email:
Keywords: LINE-1 retrotransposons; SINE retrotransposons; reverse transcriptase; copy number amplification; breast cancer progression
Received: July 17, 2013 Accepted: August 7, 2013 Published: August 9, 2013
In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons and endogenous retroviruses represent large families of repeated elements encoding reverse transcriptase (RT) proteins. Short Interspersed Nuclear Element B1 (SINE B1) retrotrasposons do not encode RT, but use LINE-1-derived RT for their retrotransposition. We previously showed that many cancer types have an abundant endogenous RT activity. Inhibition of that activity, by either RNA interference-dependent silencing of active LINE-1 elements or by RT inhibitory drugs, reduced proliferation and promoted differentiation in cancer cells, indicating that LINE-1-encoded RT is required for tumor progression. Using MMTV-PyVT transgenic mice as a well-defined model of breast cancer progression, we now report that both LINE-1 and SINE B1 retrotransposons are up-regulated at a very early stage of tumorigenesis; LINE-1-encoded RT product and enzymatic activity were detected in tumor tissues as early as stage 1, preceding the widespread appearance of histological alterations and specific cancer markers, and further increased in later progression stages, while neither was present in non-pathological breast tissues. Importantly, both LINE-1 and SINE B1 retrotransposon families undergo copy number amplification during tumor progression. These findings therefore indicate that RT activity is distinctive of breast cancer cells and that, furthermore, LINE-1 and SINE B1 undergo copy number amplification during cancer progression.
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